title: Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease.
abstract: Pre-eclampsia is a leading cause of maternal and foetal morbidity and mortality worldwide. Insufficient uteroplacental oxygenation is believed to be responsible for the disease. However, what molecular events involve in hypoxic responses and how they affect placental development remain unclear. Recently, miRNAs have emerged as a new class of molecules in response to hypoxia. We show here that the expression of microRNA-210 (mir-210) is up-regulated in patients with pre-eclampsia, as well as in trophoblast cells cultured under hypoxic conditions. Ectopic expression of mir-210 inhibited the migration and invasion capability of trophoblast cells. Ephrin-A3 and Homeobox-A9, which related with cell migration and vascular remodelling, were then experimentally validated as the functional targets of mir-210 both in vivo and in vitro. Using luciferase reporter, chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) experiments, we finally identified a new transcriptional mechanism that the overexpression of mir-210 under hypoxia was regulated by NF-κB transcriptional factor p50, apart from the well-known HIF 1α. Taken together, our study implicates an important role for mir-210 in the molecular mechanism of pre-eclampsia.
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mingyu
authors.initials: M
authors.lastname: Fei
authors.forename: Geng
authors.initials: G
authors.lastname: Xue
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yin
authors.initials: Y
authors.lastname: Jia
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.forename: Shuhan
authors.initials: S
authors.lastname: Sun
mesh_terms: D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D036384:Ephrin-A3 / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D036384:Ephrin-A3; C497442:HIF1A protein, human; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; D034741:RNA, Small Interfering; C097899:homeobox protein HOXA9